Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study

NCT01663129 | Completed

• 1 other identifier: 03-07e
• Study Type: observational
• Target: 406
• Locations: 1 country
• Sites: 12

Brief Summary

To determine the magnitude and rate of bone mass deficits following initiation of glucocorticoid therapy for the treatment of pediatric leukemia, rheumatic conditions and nephrotic syndrome, we propose a 6 year, prospective study in 12 academic, tertiary care centres across Canada. The investigators hypothesize that glucocorticoid-treated children with leukemia, rheumatic conditions and nephrotic syndrome will fail to accrue bone mass at a normal rate, and that deficits in mineral accrual will occur in a glucocorticoid dose- and duration-dependent fashion. We also hypothesize that the fracture incidence will increase with concomitant reductions in bone mass.

Conditions

Acute Lymphoblastic Leukemia; Nephrotic Syndrome; Rheumatism

Keywords

Children; Osteoporosis; Vertebral Compression Fractures; Chronic Illness; Glucocorticoids; Bone Fragility

Outcome Measures

Primary Outcomes (1)

• The magnitude and rate of total body, hip and lumbar spine bone mass deficits

  We will determine the magnitude and rate of total body, hip and lumbar spine bone mass deficits following initiation of glucocorticoid therapy, in relation to glucocorticoid dose and duration, among children with leukemia, rheumatic conditions and nephrotic syndrome. The longitudinal pattern of deficits (or gains) in bone mass will be determined for each disease state by plotting bone mass measurements taken at 6 month intervals throughout the study, with an additional 3 month measurement being recorded for patients with nephrotic syndrome.

  up to 72 months (plus at 3 months post baseline visit for the Nephrotic Syndrome Group)

Secondary Outcomes (5)

• Glucocorticoid threshold dose

  At baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 and 72-month visits

• Frequency of atraumatic fractures

  At baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 and 72-month visits

• Fracture risk

  At baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 and 72-month visits

• Magnitude of bone mass restitution

  At baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 and 72-month visits

• Handedness and lateralization of bone density

  Once during either the baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 or 72-month visits

Study Arms (3)

Leukemia Patient Group

Acute Lymphoblastic Leukemia (ALL)

Rheumatic Disease Patient Group

* Juvenile Idiopathic Arthritis (JIA) * Systemic Lupus Erythematosis * Juvenile Dermatomyositis * Scleroderma * Overlap Syndromes * Sjogren's syndrome * Sarcoidosis * Systemic Vasculitis (excluding Kawasaki's disease and Henoch-Schonlein Purpura) * Systemic vasculitis as defined by the Chapel Hill Concensus Conference on Nomenclature. Other forms of systemic vasculitis, including Giant cell (temporal) arteritis, Takayasu's arteritis, Polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, Microscopic polyangiitis, Essential cryoglobulinemic vasculitis, Cutaneous leukocytoclastic angiitis, Behcet's disease, Other vasculitis * Other rheumatic disease

Nephrotic Syndrome Patient Group

Nephrotic syndrome will be classified according to the following categories: Idiopathic nephrotic syndrome, without renal biopsy histology, presumed minimal change disease (MCD), Focal segmental glomerulosclerosis (FSGS), confirmed on biopsy, Minimal change disease, confirmed on biopsy Nephrotic syndrome with Henoch-Schonlein Purpura (HSP).

Eligibility Criteria

• Age: 1 Month - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Children will be recruited into the study following a clinical diagnosis of glucocorticoid-requiring leukemia, rheumatic disease or nephrotic syndrome, as determined by the study collaborators in each of the three sub-specialties according to their usual clinical practice. Potential participants will be identified by the attending physician (oncologist, rheumatologist or nephrologist) who will then refer the patient to the site bone designee. The bone designee (or his/her research assistant) will be responsible for determining patient eligibility and for carrying out the requirements of the study.

You may qualify if:

• Children aged \> or = 1 month to \< or = 16 years at the time of enrolment.
• Clinical diagnosis of one of the following three diseases:
• Acute lymphoblastic leukemia OR
• Rheumatic disease,OR
• Nephrotic syndrome
• Need for the first-time initiation of intravenous (IV) or oral glucocorticoid therapy (regardless of the dose or duration) for the treatment of the leukemia, nephrotic syndrome or rheumatic conditions, as determined by the attending physician. IV and oral glucocorticoids used in current clinical practice for the treatment of leukemia, nephrotic syndrome and rheumatic conditions include cortisone, hydrocortisone, methylprednisolone, prednisolone, prednisone, dexamethasone, and deflazacorte. If patients are receiving intra-articular, inhaled, intra-nasal or topical corticosteroids, these agents alone do not meet the steroid criteria for enrolment in the study. However, the use of such steroids will be captured as part of the Case Report Form.
• Only patients who are receiving glucocorticoids for the first time for the treatment of their underlying leukemia, nephrotic syndrome or rheumatic condition, will be included. Patients who have received glucocorticoids in the past for other indications (e.g. asthma), may be included in the study, provided they have not received more than 14 consecutive days of IV or oral steroids in the 12 months prior to the first initiation of steroids for their underlying leukemia, nephrotic syndrome or rheumatic condition. The pre-STOPP study use of glucocorticoids for 14 days or less, for treatment of unrelated medical conditions in the 12 months prior to the first initiation of steroids to treat the underlying leukemia, nephrotic syndrome or rheumatic conditions, will be captured in the Case Report Form.
• Informed consent.
• Ability and willingness to maintain a "Glucocorticoid Dose Diary" throughout the study.
• For menstruating females, a negative pregnancy test will be required prior to enrolment.

You may not qualify if:

• Inability to obtain baseline investigations within 30 days of the first-time initiation of glucocorticoids for the treatment of the underlying leukemia, nephrotic syndrome or rheumatic condition.
• Complete immobilization (patient confined to bed except for toileting) for more than 14 consecutive days in the 12 months prior to the initiation of glucocorticoids for the treatment of their underlying leukemia, nephrotic syndrome or rheumatic condition.
• Use of IV or oral glucocorticoids for more than 14 consecutive days, for the treatment of unrelated medical conditions, in the 12 months prior to the first initiation of steroids for the treatment of the underlying leukemia, nephrotic syndrome or rheumatic condition.
• Treatment of osteoporosis with medical therapy prior to the initial baseline visit (treatment with, for example, a bisphosphonate, calcitonin, fluoride).
• Unwillingness to utilize a medically approved method of birth control if menstruating and sexually active.

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (12)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

BC Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Winnipeg Children's Hospital

Winnipeg, Manitoba, R3E 3P4, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Centre

London, Ontario, N6C 2V5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Shriners Hospital for Children

Montreal, Quebec, H3G 1A6, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (15)

• Feber J, Gaboury I, Ni A, Alos N, Arora S, Bell L, Blydt-Hansen T, Clarson C, Filler G, Hay J, Hebert D, Lentle B, Matzinger M, Midgley J, Moher D, Pinsk M, Rauch F, Rodd C, Shenouda N, Siminoski K, Ward LM; Canadian STOPP Consortium. Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome. Osteoporos Int. 2012 Feb;23(2):751-60. doi: 10.1007/s00198-011-1621-2. Epub 2011 Apr 15.

  PMID: 21494860 RESULT

• Huber AM, Gaboury I, Cabral DA, Lang B, Ni A, Stephure D, Taback S, Dent P, Ellsworth J, LeBlanc C, Saint-Cyr C, Scuccimarri R, Hay J, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM; Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) Consortium. Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken). 2010 Apr;62(4):516-26. doi: 10.1002/acr.20171.

  PMID: 20391507 RESULT

• Halton J, Gaboury I, Grant R, Alos N, Cummings EA, Matzinger M, Shenouda N, Lentle B, Abish S, Atkinson S, Cairney E, Dix D, Israels S, Stephure D, Wilson B, Hay J, Moher D, Rauch F, Siminoski K, Ward LM; Canadian STOPP Consortium. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res. 2009 Jul;24(7):1326-34. doi: 10.1359/jbmr.090202.

  PMID: 19210218 RESULT

• Rodd C, Lang B, Ramsay T, Alos N, Huber AM, Cabral DA, Scuccimarri R, Miettunen PM, Roth J, Atkinson SA, Couch R, Cummings EA, Dent PB, Ellsworth J, Hay J, Houghton K, Jurencak R, Larche M, LeBlanc C, Oen K, Saint-Cyr C, Stein R, Stephure D, Taback S, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM; Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) Consortium. Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res (Hoboken). 2012 Jan;64(1):122-31. doi: 10.1002/acr.20589.

  PMID: 22213727 RESULT

• Alos N, Grant RM, Ramsay T, Halton J, Cummings EA, Miettunen PM, Abish S, Atkinson S, Barr R, Cabral DA, Cairney E, Couch R, Dix DB, Fernandez CV, Hay J, Israels S, Laverdiere C, Lentle B, Lewis V, Matzinger M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Wilson B, Williams K, Rauch F, Siminoski K, Ward LM. High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol. 2012 Aug 1;30(22):2760-7. doi: 10.1200/JCO.2011.40.4830. Epub 2012 Jun 25.

  PMID: 22734031 RESULT

• Siminoski K, Lee KC, Jen H, Warshawski R, Matzinger MA, Shenouda N, Charron M, Coblentz C, Dubois J, Kloiber R, Nadel H, O'Brien K, Reed M, Sparrow K, Webber C, Lentle B, Ward LM; STOPP Consortium. Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines. Osteoporos Int. 2012 Jul;23(7):1999-2008. doi: 10.1007/s00198-011-1837-1. Epub 2011 Nov 23.

  PMID: 22109742 RESULT

• Siminoski K, Lee KC, Abish S, Alos N, Bell L, Blydt-Hansen T, Couch R, Cummings EA, Ellsworth J, Feber J, Fernandez CV, Halton J, Huber AM, Israels S, Jurencak R, Lang B, Laverdiere C, LeBlanc C, Lewis V, Midgley J, Miettunen PM, Oen K, Phan V, Pinsk M, Rauch F, Rodd C, Roth J, Saint-Cyr C, Scuccimarri R, Stephure D, Taback S, Wilson B, Ward LM; Canadian STOPP Consortium National Pediatric Bone Health Working Group. The development of bone mineral lateralization in the arms. Osteoporos Int. 2013 Mar;24(3):999-1006. doi: 10.1007/s00198-012-2054-2. Epub 2012 Jun 29.

  PMID: 22744715 RESULT

• Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stephure D, Stein R, Sbrocchi AM, Rodd C, Lang B, Israels S, Grant RM, Couch R, Barr R, Hay J, Rauch F, Siminoski K, Ward LM; Canadian STOPP Consortium (National Pediatric Bone Health Working Group). Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis. J Clin Endocrinol Metab. 2015 Sep;100(9):3408-17. doi: 10.1210/JC.2015-2176. Epub 2015 Jul 14.

  PMID: 26171800 RESULT

• Ward LM, Ma J, Lang B, Ho J, Alos N, Matzinger MA, Shenouda N, Lentle B, Jaremko JL, Wilson B, Stephure D, Stein R, Sbrocchi AM, Rodd C, Lewis V, Israels S, Grant RM, Fernandez CV, Dix DB, Cummings EA, Couch R, Cairney E, Barr R, Abish S, Atkinson SA, Hay J, Rauch F, Moher D, Siminoski K, Halton J; Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) Consortium. Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study. J Bone Miner Res. 2018 Aug;33(8):1435-1443. doi: 10.1002/jbmr.3447. Epub 2018 May 22.

  PMID: 29786884 RESULT

• LeBlanc CM, Ma J, Taljaard M, Roth J, Scuccimarri R, Miettunen P, Lang B, Huber AM, Houghton K, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stein R, Sbrocchi AM, Oen K, Rodd C, Jurencak R, Cummings EA, Couch R, Cabral DA, Atkinson S, Alos N, Rauch F, Siminoski K, Ward LM; Canadian STeroid-Associated Osteoporosis in Pediatric Population (STOPP) Consortium. Incident Vertebral Fractures and Risk Factors in the First Three Years Following Glucocorticoid Initiation Among Pediatric Patients With Rheumatic Disorders. J Bone Miner Res. 2015 Sep;30(9):1667-75. doi: 10.1002/jbmr.2511. Epub 2015 May 26.

  PMID: 25801315 RESULT

• Ma J, Siminoski K, Alos N, Halton J, Ho J, Lentle B, Matzinger M, Shenouda N, Atkinson S, Barr R, Cabral DA, Couch R, Cummings EA, Fernandez CV, Grant RM, Rodd C, Sbrocchi AM, Scharke M, Rauch F, Ward LM; Canadian STOPP Consortium. The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures. J Clin Endocrinol Metab. 2015 Mar;100(3):1018-27. doi: 10.1210/jc.2014-3096. Epub 2014 Dec 11.

  PMID: 25494661 RESULT

• Jaremko JL, Siminoski K, Firth GB, Matzinger MA, Shenouda N, Konji VN, Roth J, Sbrocchi AM, Reed MH, O'Brien MK, Nadel H, McKillop S, Kloiber R, Dubois J, Coblentz C, Charron M, Ward LM; Canadian STOPP Consortium National Pediatric Bone Health Working Group. Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study. Pediatr Radiol. 2015 Apr;45(4):593-605. doi: 10.1007/s00247-014-3210-y. Epub 2015 Apr 1.

  PMID: 25828359 RESULT

• Shiff NJ, Brant R, Guzman J, Cabral DA, Huber AM, Miettunen P, Roth J, Scuccimarri R, Alos N, Atkinson SA, Collet JP, Couch R, Cummings EA, Dent PB, Ellsworth J, Hay J, Houghton K, Jurencak R, Lang B, Larche M, Leblanc C, Rodd C, Saint-Cyr C, Stein R, Stephure D, Taback S, Rauch F, Ward LM; Canadian Steroid-associated Osteoporosis in the Pediatric Population Consortium. Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases. Arthritis Care Res (Hoboken). 2013 Jan;65(1):113-21. doi: 10.1002/acr.21785.

  PMID: 22826190 RESULT

• Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM; Canadian STOPP Consortium. Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int. 2014 Feb;25(2):627-37. doi: 10.1007/s00198-013-2466-7. Epub 2013 Aug 16.

  PMID: 23948876 RESULT

• Siminoski K, Lentle B, Matzinger MA, Shenouda N, Ward LM; Canadian STOPP Consortium. Observer agreement in pediatric semiquantitative vertebral fracture diagnosis. Pediatr Radiol. 2014 Apr;44(4):457-66. doi: 10.1007/s00247-013-2837-4. Epub 2013 Dec 10.

  PMID: 24323185 RESULT

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Nephrotic Syndrome; Rheumatic Diseases; Osteoporosis; Chronic Disease

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Bone Diseases, Metabolic; Bone Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leanne M Ward, MD FRCPC

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pediatric Bone Health Clinical and Research Programs

Study Record Dates

• First Submitted: August 8, 2012
• First Posted: August 13, 2012
• Study Start: January 1, 2005
• Primary Completion: March 6, 2014
• Study Completion: March 6, 2014
• Last Updated: July 20, 2018

Record last verified: 2018-07

Locations

CA (12)